Roberto Sitia contributed to the discovery of some of the molecular mechanisms that allow cells to secrete abundant proteins of the highest quality for the desired time. Having focused on antibodies, his findings have important implications in biotechnology (production of human proteins) and medicine (treatment of myeloma and ER storage disorders). Sitia’s contributions includes:

• Discovery of thiol-mediate retention, a mechanisms of protein quality control in the secretory pathway, by which an exposed thiol acts as a 3-way switch to coordinate assembly, retention or degradation of secretory proteins.
• Identification of the main mechanisms of disulfide bond formation in the human ER
• Elucidation of how B cells reshape redox regulation during plasma cell differentiation to sustain IgM production.
• Identification of AQP8 as H2O2 transporter across the plasma membrane and its regulation.
• Identification of a novel, unconventional secretory route used by proteins that lack a signal peptide, such has IL-1, thioredoxin and HIV-tat.
• Studies on the biogenesis of Russell bodies.
• Description of the morpho-functional metamorphosis that hallmarks terminal B cell differentiation into plasma cells and dissection of the underlying molecular mechanisms
• Discovery that an unfavorable ratio between proteasomal load and capacity (proteostenosis) makes plasma cells uniquely sensitive to proteasome inhibitors, with profound clinical implications for myeloma and lupus.